title: Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism.
abstract: OBJECTIVE
  To determine whether Fusobacterium nucleatum's ability to invade cells allows the bacteria to activate pro-inflammatory response through cytosolic pattern recognition receptors, independent of surface Toll-like receptors (TLRs).
  
  
  METHODS
  HEK293T cells, which lack endogenous TLRs, and overexpressing dominant negative myeloid differentiation primary response gene 88 (MyD88DN) protein, were infected with F. nucleatum and the production of interleukin-8 (IL-8) was determined. The necessity for intracellular invasion of the bacteria for cytokine production was also investigated by blocking bacterial invasion with cytochalasin D. The roles of NFĸB and p38 mitogen-activated protein kinase (MAPK) and nucleotide-binding oligomerization domain-1 (NOD-1) signalling pathways in F. nucleatum-induced IL-8 secretion were determined.
  
  
  RESULTS
  Fusobacterium nucleatum-infected HEK293T cells produced IL-8 independent of the MYD88 signalling. This response was inhibited by preventing F. nucleatum invasion into HEK293T cells. p38 MAPK but not the NFĸB signalling pathway was required for F. nucleatum-mediated IL-8 production. HEK293T cells expressed NOD-1 but not NOD-2. Yet, inhibition of NOD-1 signalling did not affect F. nucleatum-induced IL-8 secretion.
  
  
  CONCLUSIONS
  Fusobacterium nucleatum invasion led to cytokine production, which is mediated by the p38 MAPK signalling but independent of TLRs, NOD-1, NOD-2 and NFĸB signalling.
authors.affiliation: Faculty of Dentistry, National University of Singapore, Singapore City, Singapore.
authors.forename: S Y
authors.initials: SY
authors.lastname: Quah
authors.forename: G
authors.initials: G
authors.lastname: Bergenholtz
authors.forename: K S
authors.initials: KS
authors.lastname: Tan
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D016967:Fusobacterium nucleatum / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism / Q000502:physiology*
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
keywords: Fusobacterium nucleatum; Toll-like receptors; bacterial invasion; nucleotide-binding oligomerization domain-1; nucleotide-binding oligomerization domain-2; p38 mitogen-activated protein kinase